Bone marrow transplantation has the potential of providing a complete cure of the disease symptoms of hemoglobinopathies. Successful application of mismatched (related-haploidentical) bone marrow transplantation to patients with sickle cell disease or a thalassemia requires that allochimerism be achieved and stabilized in the bone marrow with less morbidity and mortality than are being experienced in existing mismatched bone marrow transplantation (BMT) protocols. This goal requires use of less total body radiation and less drug myeloablation in support of the transplantation. Mixed chimeric bone marrow states have been achieved and stabilized in mice through the use of psoralen photochemically treated donor leukocytes which are blocked in their proliferative capabilities, but which retain their immunological activities. Model mouse bone marrow transplantation experiments, in a complete MHC mismatch setting, are proposed here which will prove, under low dose myeloablative radiation conditions and in the absence of myeloablative and immunosuppressive drugs, that S-59 (a psoralen) photochemically treated (S-59 PCT) T-cell add-backs promote and stabilize allochimerism with greatly reduced risk of graft versus host disease (GVHD). In the first year, the mouse experiments will be performed at the Medical College of Wisconsin. The MHC-mismatched model consists of C57BL/6 (H-2b) donors and sub-lethally irradiated AKR/J (H-2k) as recipients. GVH reactivity is primarily directed against MHC class I and class II disparities. In the second and third years, in collaboration with the Children's Hospital Oakland Research Institute, thalassemia mouse models involving the same mouse strains will be transplanted and the therapeutic value of BMT in improving the anemias will be evaluated. A mouse sickle cell model with a poorly defined genetic background will also be studied, because it will most accurately mimic the transplantion situation with humans.